Administration of 5-HT-1B agonist ameliorates pseudodementia induced by depression in rats

Abstract

Major depressive disorder (MDD) is the leading cause of memory impairment in general population. The serotonin hypothesis provides a target model for the treatment of depression and depression-associated memory loss. 5- HT-1B receptor is suggested as a potential candidate in the pathophysiology of depressive illness. Dysfunction of 5-HT1B receptors has been observed previously in depressive patients. Zolmitriptan, 5-HT-1B agonist is clinically recommended for the treatment of migraine. However, in present study this drug was tested as a potential treatment for depression and associated memory loss by altering the serotonergic function at receptor level. Rats (n=24) were equally divided into unstressed and stressed groups. Depression was induced by 19 days of restraint stress for 4 h which was followed by forced swim test and pattern separation test to assess depressive symptoms and memory impairment, respectively. The initial sign of depression-associated memory loss involves impaired pattern separation which is regarded as pseudodementia. In this study stressed rats showed depression- and pseudodementia-like symptoms. After the induction of depression, rats were treated with zolmitriptan at a dose of 0.3 mg/kg which resulted in a significant attenuation of depression and depression-associated memory impairment. Results are discussed with reference to the modulation of function of 5-HT-1B receptor following the administration of exogenous agonist.